ANTITUMOR-ACTIVITY OF HEXAMETHYLMELAMINE ON HUMAN TUMOR XENOGRAFTS SERIALLY TRANSPLANTED IN NUDE-MICE

The antitumor activity of hexamethylmelamine (HMM) was evaluated using four human tumor xenografts serially transplanted in nude mice. HMM w as dissolved in 0.2 ml of 1% hydroxypropyl cellulose per mouse and adm inistered perorally daily, except on Sunday, for 4 weeks, giving an es timated maximum tolerated dose (MTD) of HMM of 75 mg/kg. The MX-1 cell line showed dose-dependent sensitivity to HMM and was completely erad icated by treatment at the MTD. The minimum effective dose of HMM agai nst MX-1 was calculated to be 22.1 mg HMM/kg, resulting in the chemoth erapeutic index of 3.4. The demethylated derivatives of HMM, pentameth ylmelamine and tetramethylmelamine, were also effective against MX-1, whereas trimethylmelamine was ineffective. The effect of HMM was more marked when the drug was administered on day 1 after tumor inoculation , compared with administration during the exponential growth phase. HM M is thought to be a promising agent for the treatment of several type s of human carcinoma, producing active metabolites in vivo after peror al administration.